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Characterization of NF-kB-mediated inhibition of catechol-O-methyltransferase.

Publication ,  Journal Article
Tchivileva, IE; Nackley, AG; Qian, L; Wentworth, S; Conrad, M; Diatchenko, LB
Published in: Mol Pain
March 16, 2009

BACKGROUND: Catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, has recently been implicated in the modulation of pain. Specifically, low COMT activity is associated with heightened pain perception and development of musculoskeletal pain in humans as well as increased experimental pain sensitivity in rodents. RESULTS: We report that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) downregulates COMT mRNA and protein in astrocytes. Examination of the distal COMT promoter (P2-COMT) reveals a putative binding site for nuclear factor kappaB (NF-kappaB), the pivotal regulator of inflammation and the target of TNFalpha. Cell culture assays and functional deletion analyses of the cloned P2-COMT promoter demonstrate that TNFalpha inhibits P2-COMT activity in astrocytes by inducing NF-kappaB complex recruitment to the specific kappaB binding site. CONCLUSION: Collectively, our findings provide the first evidence for NF-kappaB-mediated inhibition of COMT expression in the central nervous system, suggesting that COMT contributes to the pathogenesis of inflammatory pain states.

Duke Scholars

Published In

Mol Pain

DOI

EISSN

1744-8069

Publication Date

March 16, 2009

Volume

5

Start / End Page

13

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Rats
  • Promoter Regions, Genetic
  • Neurology & Neurosurgery
  • NF-kappa B
  • NF-KappaB Inhibitor alpha
  • I-kappa B Proteins
  • Humans
  • Down-Regulation
  • Cloning, Molecular
 

Citation

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ICMJE
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Tchivileva, I. E., Nackley, A. G., Qian, L., Wentworth, S., Conrad, M., & Diatchenko, L. B. (2009). Characterization of NF-kB-mediated inhibition of catechol-O-methyltransferase. Mol Pain, 5, 13. https://doi.org/10.1186/1744-8069-5-13
Tchivileva, Inna E., Andrea G. Nackley, Li Qian, Sean Wentworth, Matthew Conrad, and Luda B. Diatchenko. “Characterization of NF-kB-mediated inhibition of catechol-O-methyltransferase.Mol Pain 5 (March 16, 2009): 13. https://doi.org/10.1186/1744-8069-5-13.
Tchivileva IE, Nackley AG, Qian L, Wentworth S, Conrad M, Diatchenko LB. Characterization of NF-kB-mediated inhibition of catechol-O-methyltransferase. Mol Pain. 2009 Mar 16;5:13.
Tchivileva, Inna E., et al. “Characterization of NF-kB-mediated inhibition of catechol-O-methyltransferase.Mol Pain, vol. 5, Mar. 2009, p. 13. Pubmed, doi:10.1186/1744-8069-5-13.
Tchivileva IE, Nackley AG, Qian L, Wentworth S, Conrad M, Diatchenko LB. Characterization of NF-kB-mediated inhibition of catechol-O-methyltransferase. Mol Pain. 2009 Mar 16;5:13.
Journal cover image

Published In

Mol Pain

DOI

EISSN

1744-8069

Publication Date

March 16, 2009

Volume

5

Start / End Page

13

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Rats
  • Promoter Regions, Genetic
  • Neurology & Neurosurgery
  • NF-kappa B
  • NF-KappaB Inhibitor alpha
  • I-kappa B Proteins
  • Humans
  • Down-Regulation
  • Cloning, Molecular